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Final report of work done on the Minor Research Project
(MRP(S)-1127/11-12/KAMY013/UGC-SWRO)
Synthesis and characterization of biologically active metal complexes
Submitted to
Deputy Secretary
South Western Regional Office
PK Block, Palace road, Gandinagar, Bangalore-560009
By
Dr. B.K.Kendagannaswamy, MSc.,Ph.D
Assistant Professor, Department of Chemistry.
JSS College of Arts, Commerce and Science, Ooty road
Mysore-570025
(An autonomous college under university of Mysore; Re-accredited by NAAC with „A‟ grade)
Phone;0821-2548236; Fax;0821-2548238
Email;[email protected]
UNIVERSITY GRANTS COMMISSION
BAHADUR SHAH ZAFAR MARG
NEW DELHI – 110 002.
Final Report of the work done on the Minor Research Project.
1. Project report No. First
2. UGC Reference No. MRP(S)-1127/11-12/KAMY013/UGC-SWRO
3. Period of report: 13-07-2012 to 30-12-2014
4. Title of research project Synthesis and characterization of biologically
active metal complexes
5. (a) Name of the Principal Investigator Dr. B.K. Kendagannaswamy
(b) Department. and University/College where
work has progressed
Department of chemistry, JSS College of Arts,
Commerce & Science, Ooty road,Mysore-25
6. Effective date of starting of the project 20-07-2012
7. Grant approved and expenditure incurred during the period of the report
a. Total amount approved Rs.
Rs1,50,000/-
b. Total expenditure Rs Rs 1,52,506/-
c. Report of the work done: (Please attach a
separate sheet)-
enclosed
I. Brief objective of the project a) Synthesis of Schiff base ligands and their
metal complexes.
b) Characterization of the prepared ligands by
using spectroscopic studies (IR, 1H-NMR
and MS) elemental analyses, magnetic
moments and molar conductance.
c) In order to check the biological activities of
the prepared ligands and their metal
complexes, we have planned to conduct
antibacterial, antifungal and anthelmentic
studies
II. Work done so far and results achieved and
publications, if any, resulting from the work (Give
details of the papers and names of the journals in
which it has been published or accepted for
publication
We have synthesized several Schiff base ligands
and their metal complexes. All the prepared
compounds were characterized by spectroscopic
analysis. In addition, we have also published two
research article entitled “Synthesis and in vitro
activity of quinolin-5-ylamine derivatives” in a peer-
reviewed Journal “Current Chemistry Letters”
‘Investigation of Antioxidant Activity of 3, 5-
Dimethoxyaniline Derivatives’ in a peer
reviewed Journal of Applicable Chemistry, 2014,
3 (5): 2131-2137(Copy is attached).
III. Has the progress been according to original
plan of work and towards achieving the objective.
if not, state reasons
Yes, according to the original plan of work.
IV. Please indicate the difficulties, if any,
experienced in implementing the project
Not Applicable
V. If project has not been completed; please
indicate the approximate time by which it is likely
to be completed. A summary of the work done for
the period (Annual basis) may please be sent to the
Commission on a separate sheet
Not Applicable
VI. If the project has been completed, please
enclose a summary of the findings of the study.
Two bound copies of the final report of work done
may also be sent to the Commission
Status of the project- completed
Summary of the findings of the enclosed.
Two bound copies of the final report of work done
is enclosed
VII. Any other information which would help in
evaluation of work done on the project. At the
completion of the project, the first report should
indicate the output, such as (a) Manpower trained
(b)Ph.D awarded (c) Publication of results (d)
Other impact, if any
Students trained.
Two papers Published
SIGNATURE OF THE SIGNATURE OF THE
PRINCIPAL INVESTIGATOR PRINCIPAL
Summary report about proposed research project:
Introduction
Modern trends in the area of coordination chemistry involve studies on the synthesis,
structure and applications. The role of metal ions in living systems is well established in recent
years. It has been recognized that inorganic biochemistry is a bridge between the academic
disciplines viz., biochemistry and inorganic chemistry. In fact, biochemistry has been considered as
the coordination chemistry of living systems [1]. This dependence is well exemplified by the
observation that one third of all enzymes have a metal ion as essential component [2]. Several
reviews, monographs etc., are available on the inorganic aspects of biochemistry [3-5]. As metal
ions play such an important role in biological systems it is to be expected that the various aspects
of coordination will be studied with intense interest.
The reasons for the persistent interest in the complexes are many, but the important among
them must be their role in various biochemical, pharmaceutical, industrial and chemical processes.
Certain coordination compounds, which are occur in nature of biological importance. The
participation of metallo proteins in respiratory, photosynthetic, nitrogen fixation, biosynthetic and
metabolic processes is essential to the foundations of life. Several cobalt complexes are important
as models to oxygen binding involved in biological systems, cobalt is also present in enzymes
related to vitamin B12. A number of copper proteins including enzymes such as ascorbic acid
oxidase, cytochrome oxidase etc., have been isolated.
Coordination complexes have a long history of use as chemotherapeutic agents. The
successful application of inorganic complexes as drugs involves the recognition of their
bioinorganic modes of action coupled with the traditional pharmacokinetic parameters of uptake,
distribution and excretion. Further, the rational approaches to chemotherapy and particularly the
notion of selective toxicity [6, 7] must be placed in an inorganic context. The concept of selective
toxicity, and its scientific basis, is of particular use in describing the actions of drugs on an
invading organisms, be it viral, bacterial, parasitic or ultimately malignant tumours caused by the
cancerous growth of the host‟s cells. The achievement of some form of selectivity is critical to the
successful use of any agent as a drug or modifier of biological response.
Bacterial, viral and malignant tumour (cancer) remains the most life threatening, refractory
and global killer diseases around the world. Present therapy involving organic moieties as
therapeutic agents is increasingly getting marginalized due to rapid emergence of drug resistance,
limited target specificity and difficult to achieve therapeutic drug levels. Consequently metallo
drugs offer unique advantages in overcoming these difficulties. These are the compounds
incorporating biologically relevant transition metal ions an integral part of their structural scaffold
and possess clinical and therapeutic value. They can provide synergized bioavailability through
increased liposolubility, enhanced biological activity and selective targeting of certain proteins/
receptors and activity against drug-resistant species.
The predominant role of DNA in cellular replication and transmission of genetic
information makes the nucleic acids a primary target for drug action, and many drugs are
considered to act fundamentally at this level. In the case of metals (metal-aqua complexes) and
other metal complexes, the subject of their interaction with DNA is relevant for a number of
reasons. These systems range from in vivo aspect such as the endogenous presence in the nucleus
of metal ions, the role of zinc in RNA polymerase, the mutagenesis and eventual carcinogenesis of
metal ions, the diverse uses of metal ions as probes of polynucleotide structure, as well as the
cytotoxic effects of metal-complexes.
There has been an increasing interest in the synthesis of novel model metal coordination
compounds to mimic biological reactions. These investigations constitute one of the major lines of
pursuit in bioinorganic chemistry concept. These model studies have been useful to understand the
role of metal ions in specified coordination geometries dictating the course and nature of reaction
in biological systems. One of the successful routes to tackle this problem is through the
investigations on structure-property correlation of new complexes. It is, therefore, worthwhile t
study on the synthesis of some biologically active ligands and also the isolation of their novel
metal complexes.
In coordination chemistry, Schiff bases have a significant role as ligands still a century
after their discovery [8]. The importance of Schiff bases and their metal complexes are important
as biochemical, electrochemical, analytical, antifungal and antibacterial activities and redox
catalysts. A comprehensive review [9] covers much of the Schiff base chemistry known up to 2007
and it has been followed by others. Structure and mechanism of the formation of metal complexes
and stereochemistry of four coordinate chelate compounds from Schiff bases and their analogues
have been discussed in a review [10] with 250 references.
Schiff-base metal complexes have been known since the mid nineteenth century and even
before the general preparation of Schiff base ligands themselves. Metal complexes of Schiff bases
have occupy a central place in the development of coordination reaction chemistry, the work
Jorgense and Werner. Ettlings isolated a dark green crystalline product from the reaction of cupric
acetate, salicylaldehyde and aqueous ammonia. Schiff has synthesized complexes of metal-
salicylaldehyde with primary amines. Subsequently, Schiff isolated complexes from the
condensates of urea and salicylaldehydes. Delepine has prepared complexes by reacting metal
acetate salicyladehydes and a primary amine in an alcohol and demonstrated a 2:1 stoichiometry.
However, there was no comprehensive, systematic study until the preparative work of Pfeiffer and
associates.
Apart from biological applications of metal complexes, the coordination compounds of azo,
formazan, azomethine, nitroso, anthraquinone and phthalocyanine ligands find important
applications in the field of photography, catalysis and some modern high technology industries,
such as electronics. Chromium and cobalt complexes of azo-dye stuffs were largely used in the
homogeneous and asymmetric catalysis. Other metal complexes were used as catalysts in olefin
hydroxylation, hydrogenation, cyclopropanation , cyclo addition and allylic alkylation reactions.
Recently reported review article has covered all aspects of metal-based catalyst preparation,
physical properties and its applications [11].
Though significant advances have been made in the field of coordination chemistry, there
is still scope on the study of complexes whose structures and reactivity are less understood. It is,
therefore, considered worthwhile to study on the synthesis, structural elucidation and biological
activity of a new series of complexes of biological importance.
Synthesis of ligands
In the present investigation, we have synthesized Schiff‟s base ligands of quinazolinone
and also characterized by elemental analysis, Infrared, 1H-NMR and mass spectral studies.
Figure 1: Structures of synthesized Schiff base.
Table 1: Analytical and physical data of quinazolin-4(3H)-one Schiff base ligands.
Compound
Ligand
Melting
Point
(°C)
Yield
(%)
Elemental found (calculated)
Molecular
Formula
(Mol. Wt)
C (%)
H (%)
N (%)
S(%)
L1 C16H13N3O2
(279)
167-169
71
68.43
(68.5)
4.58
(4.61)
14.9
(15.02)
-
L2 C15H12N4O2
(264)
175-177
63
68.18
(68.27)
4.28
(4.31)
21.22
(21.32)
-
L3 C17H15N3O3
(309)
215-217
61
66.01
(66.12)
4.93
(5.03)
13.58
(13.79)
-
L4 C16H15N3OS
(297) 183-185 79
64.62
(65.13)
5.08
(5.14)
14.13
(15.61)
10.77
(10.91)
0
110
50
100
4000 600100020003000
%T
Wavenumber [cm-1]
0
110
50
100
4000 600100020003000
%T
Wavenumber [cm-1]
L1 L2
0
110
50
100
4000 600100020003000
%T
Wavenumber [cm-1]
-10
110
0
50
100
4000 600100020003000
%T
Wavenumber [cm-1]
L3 L4
Figure 2: IR spectra of synthesized ligands.
L1
L2
L3
L4
Figure 3: 1H-NMR spectra of ligands.
L1 L2
L3 L4
Figure 4: Mass spectra of ligands.
Synthesis of metal complexes
The metal complexes were prepared in 1:2 ratio using above prepared Schiff base ligands and
1,10-phenanthroline.
M=Cu(II), Co(II), Cr(III),Zn(II).
Figure 6: Structure of metal complex.
Synthesis of Schiff bases of quinolin-5-ylamine with different aldehydes
Scheme 1: Synthetic route of quinolin-5-ylamine derivatives.
Figure 5: Structures of synthesized quinolin-5-ylamine analogues.
This part of work has been published in CURRENT CHEMISTRY LETTERS. In this article we
have shown the antioxidant activities of quinolin-5-ylamine analogues. All the compounds showed
DPPH radical scavenging activity.
References:
1. J.M. Wood, Naturewissenschaften, 62, 357 (1975).
2. B.L. Vallee and W.E.C. Wacker, The Proteins, (Ed. W, Newrath), vol 5, Academic Press, New
York, p. 1 (1970).
3. R.W. Hay and D.R. Williams, Specialist Periodical Reports; Amino Acids, Peptides and Proteins,
The Chemical Society, London (1982).
4. M.W. Dennis, S. Stojan and B. Sarkar, Coord. Chem. Rev., 122, 171 (1993).
5. K. Hussain Reddy, Bio-inorganic chemistry, New Age International Ltd., New Delhi (2003).
6. A. Albert, Selective Toxicity, 6th
Edn., Champan and Hall, London (1979).
7. N. Farell, Transition Metal Complexes as Drugs and Chemotherapeutic Agents, Kluwer Academic
Publishers (1989).
8. H. Temel, U. Çakir and H.Y. Uðra, Russian Journal of Inorganic Chemistry, 46, 1846 (2001).
9. P.A.Vigato, S. Tamburini and L. Bertolo, Coordination Chemistry Reviews, 251, 1311 (2007).
10. J.S. Casas, M.S. Garcia-Tasende and J. Sordo, Coordination Chemistry Reviews, 209, 197 (2000).
11. A. Stephen, K. Hashmi and Miriam Buhrle, Aldrichchemica, 43, 27 (2010).
Investigation of Antioxidant Activity of 3,5-Dimethoxyaniline
Derivatives
INTRODUCTION
In recent years, there has been an increased interest in the application of antioxidants to
medical treatment as information is constantly gathered linking the development of human
diseases to oxidative stress. Free radicals play a role in the pathogenesis of chronic degenerative
diseases including cancer, autoimmune, inflammatory, cardiovascular and neurodegenerative
diseases and aging [1-4]. It is also known that oxidative stress can be induced by a wide range of
environmental factors including UV stress, pathogen invasion, herbicide action and oxygen
shortage [5]. Owing to these facts, synthetic and natural compounds with potential antioxidant
activity are receiving increased attention in biological research, medicine and pharmacy [6].
Schiff bases are characterized by the imine group which is important in elucidating the
mechanism of transamination and racemisation reactions in biological systems [7]. Due to the
great flexibility and diverse structural aspects, a wide range of Schiff bases have been synthesized
and their complexation behaviors have been studied [8]. They have been synthesized from a
variety of compounds such as amino thiazoles, 2-hydroxy-1-napthalaniline, amino sugars, aromatic
aldehydes, ketones, isatin, triazole ring, thiosemicarbazides, amino acids and pyrazolone [9, 10].
Antibacterial, antifungal, antitumor and anticancer activities of some Schiff bases have been
reported and they are active against a wide range of organisms [11]. Some Schiff bases bearing
aryl groups or heterocyclic residues possessing excellent biological activities have attracted the
attention of many researchers in recent years [12]. The Schiff bases formed from aromatic
aldehydes, ketones and their derivatives are quite stable. Many Schiff bases are known to be
medicinally important and are used to design medicinal compounds [13]. Treatment of 1,2-
indanedione with 3,5-dimethoxybenzenamine in benzene afforded several products have been
reported [14]. Synthesis of poly(2,5-dimethoxyaniline) and poly(aniline-Co-2,5-dimethoxyaniline)
has been reported [15]. Crystal structure of some novel compounds from 3,5-dimethoxyaniline
have been reported [16]. In this respect, the present paper reports the preparation and antioxidant
activity of a new class of Schiff bases, 3a-g.
MATERIALS AND METHODS
All solvents and reagents were purchased from Sigma-Aldrich Chemicals Pvt. Ltd., India.
Melting points were determined using SELACO-650 hot stage melting point apparatus and were
uncorrected. Elemental analyses were recorded on VarioMICRO superuser V1.3.2 Elementar. The
UV spectra were recorded using Analytik Jena Specord 50 UV–vis spectrophotometer. FT-IR
spectra were recorded using a Jasco FTIR-4100 series. 1H-NMR spectra were recorded on
Shimadzu AMX 400-Bruker, 400 MHz spectrometer using DMSO-d6 as a solvent and TMS as
internal standard (chemical shift in ppm). All the compounds 3a-g was prepared according to the
reported procedure [17].
General procedure for the preparation of 3,5-dimethoxyaniline derivatives 3a-g: Equimolar
concentrations of different aldehydes (0.003 mol) and 3,5-dimethoxyaniline (0.003 mol) were
stirred for 4-6 hr at room temperature in absolute ethanol (25 ml) and then 2-3 drops of
concentrated sulfuric acid was added to the mixture. The progress of the reaction was monitored
by TLC until the reaction was complete. It was cooled to 0 °C, and the precipitate was filtered,
washed with diethyl ether and the residue was recrystallized from methanol.
N-(2-Chloro-6-fluorobenzylidene)-3,5-dimethoxybenzenamine (3a): The general
experimental procedure described above afforded 3a, and the product obtained from 3,5-
dimethoxybenzenamine (1) (0.50 g) and 2-chloro-6-fluorobenzaldehyde (2a) (0.47 g). 1H-NMR
(400 MHz, DMSO-d6): δ 8.65 (s, 1H, HC=N), 7.42-7.40 (m, 3H, Ar-H), 6.53-7.12 (s, 3H, Ar-H),
3.31 (s, 6H, OCH3). Anal. Calcd. for C15H13ClFNO2: C, 61.34; H, 4.46; N, 4.77; Found: C, 61.22;
H, 4.58; N, 4.56 %.
2-((3,5-Dimethoxyphenylimino)methyl)phenol (3b): The general experimental procedure
described above afforded 3b, and the product obtained from 3,5-dimethoxybenzenamine (1) (0.50
g) and 2-hydroxybenzaldehyde (2b) (0.37 ml). 1H-NMR (400 MHz, DMSO-d6): δ 8.60 (s, 1H,
HC=N), 7.921-7.86 (m, 4H, Ar-H), 6.61-7.10 (s, 3H, Ar-H), 6.42 (s, 1H, OH), 3.34 (s, 6H, OCH3).
Anal. Calcd. for C15H15NO3: C, 70.02; H, 5.88; N, 5.44; Found: C, 70.25; H, 5.78; N, 5.56 %.
4-((3,5-Dimethoxyphenylimino)methyl)-2-methoxyphenol (3c): The general experimental
procedure described above afforded 3c, and the product obtained from 3,5-dimethoxybenzenamine
(1) (0.50 g) and 4-hydroxy-3-methoxybenzaldehyde (2c) (0.46 g). 1H-NMR (400 MHz, DMSO-
d6): δ 8.68 (s, 1H, HC=N), 7.97 (s, 1H, Ar-H), 7.84 (d, 1H, Ar-H), 7.75 (d, 1H, Ar-H), 6.61-7.11
(s, 3H, Ar-H), 6.54 (s, 1H, OH), 3.35 (s, 9H, OCH3). Anal. Calcd. for C16H17NO4: C, 66.89; H,
5.96; N, 4.88; Found: C, 66.72; H, 5.78; N, 4.66 %.
4-((3,5-Dimethoxyphenylimino)methyl)phenol (3d): The general experimental procedure
described above afforded 3d, and the product obtained from 3,5-dimethoxybenzenamine (1) (0.50
g) and 4-hydroxybenzaldehyde (2d) (0.37 g). 1H-NMR (400 MHz, DMSO-d6): δ 8.53 (s, 1H,
HC=N), 7.94 (d, 2H, Ar-H), 7.44 (d, 2H, Ar-H), 6.72-7.22 (s, 3H, Ar-H), 6.42 (s, 1H, OH), 3.31 (s,
6H, OCH3). Anal. Calcd. for C15H15NO3: C, 70.02; H, 5.88; N, 5.44; Found: C, 70.25; H, 5.78; N,
5.36 %.
N-(4-Ethoxybenzylidene)-3,5-dimethoxybenzenamine (3e): The general experimental
procedure described above afforded 3e, and the product obtained from 3,5-dimethoxybenzenamine
(1) (0.50 g) and 4-ethoxybenzaldehyde (2e) (0.41 ml). 1H-NMR (400 MHz, DMSO-d6): δ 8.81 (s,
1H, HC=N), 8.44 (d, 2H, Ar-H), 7.99 (d, 2H, Ar-H), 7.85 (s, 1H, Ar-H), 7.55 (s, 1H, Ar-H), 7.28
(s, 1H, Ar-H), 4.13 (q, 2H, CH2),2.92 (s, 6H, OCH3), 2.36 (t, 3H, CH3). Anal. Calcd. for
C17H19NO3: C, 71.56; H, 6.71; N, 4.91; Found: C, 71.75; H, 6.78; N, 4.76 %.
(3,4-Dimethoxy-benzylidene)-(3,5-dimethoxy-phenyl)-amine (3f): The general
experimental procedure described above afforded 3f, and the product obtained from 3,5-
dimethoxyaniline (1) (0.50 g) and 3,4-dimethoxybenzaldehyde (2f) (0.50 g). 1H-NMR (400 MHz,
DMSO-d6): δ 8.40 (s, 1H, HC=N), 7.10 (d, 1H, Ar-H), 7.03 (s, 1H, Ar-H), 6.75 (d, 1H, Ar-H), 6.28
(s, 3H, Ar-H), 3.64 (s, 12H, OCH3). Anal. Calcd. for C17H19NO4: C, 67.76; H, 6.36; N, 4.65;
Found: C, 67.85; H, 6.28; N, 4.46 %.
(3,5-Dimethoxy-phenyl)-(3,4-dimethyl-benzylidene)-amine (3g): The general experimental
procedure described above afforded 3g, and the product obtained from 3,5-dimethoxyaniline (1)
(0.50 g) and 3,4-dimethylbenzaldehyde (2g) (0.40 g). 1H-NMR (400 MHz, DMSO-d6): δ 8.42 (s,
1H, HC=N), 7.12 (d, 1H, Ar-H), 7.00 (s, 1H, Ar-H), 6.81 (d, 1H, Ar-H), 6.26 (s, 3H, Ar-H), 3.60
(s, 6H, OCH3), 2.30 (s, 6H, CH3). Anal. Calcd. for C17H19NO2: C, 75.81; H, 7.11; N, 5.20; Found:
C, 75.85; H, 7.28; N, 5.36 %.
Antioxidant activity: The free radical scavenging activity of the compounds was studied in
vitro by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assay method [18]. Stock solution of the drug was
diluted to different concentrations in the range of 100-200 μg/ml in methanol. Methanolic solution
of the compounds (2 ml) was added to 0.003 % (w/v) methanol solution of DPPH (1 ml). The
mixture was shaken vigorously and allowed to stand for 30 min. Absorbance at 517 nm was
determined and the percentage of scavenging activity was calculated. Ascorbic acid was used as
the standard drug. The inhibition ratio (I %) of the tested compounds was calculated according to
the following equation: I % = (Ac-As) / Ac × 100, where Ac is the absorbance of the control and As
is the absorbance of the sample. The concentration of compounds providing 50 % scavenging of
DPPH· (IC50) was calculated from the plot of percentage inhibition against concentration (µg/mL).
All tests and analyses were done in triplicate and the results were averaged.
RESULTS AND DISCUSSION
The reaction of 3,5-dimethoxyaniline (1) with different aldehydes, were carried out in the
presence of ethanol as solvent with a good yield ranging from 70- 82 %. Compounds were
characterized by UV-visible, FT-IR and
1H NMR spectral studies. The chemical structures and
physical data of all the compounds are given in Table 1. The electronic absorption spectra of the
compounds showed new bands, and the appearance of longer wavelength absorption band in the
UV-visible region confirms the formation of compounds. The synthetic route of the compounds is
outlined in Scheme 1.
EtOH, H+
r.t., 4-6 hr
NH2
OCH3H3CO
N
OCH3H3CO
CH
R
1 2(a-g) 3(a-g)
R CHO
Scheme 1
Table-1: Chemical structures and physical data of 3a-g
Compound R Structure Mol. Wt. Yield
(%)
UV-
visible
M.R
(°C)
3a Cl
F
N
OCH3H3CO
CH
Cl
F
293.7 70.0 450 107-109
3b HO
N
OCH3H3CO
CH
HO
257.3 72.4 410 102-104
3c OCH3
OH
N
OCH3H3CO
CH
OCH3
OH
287.3 79.0 460 105-107
3d OH
N
OCH3H3CO
CH
OH
257.3 82.0 397 110-112
3e O
N
OCH3H3CO
CH
O
285.1 78.4 373 116-118
3f
OCH3
OCH3
N
OCH3H3CO
CH
OCH3
OCH3
301.4 78.4 398 156-158
3g
CH3
CH3
N
OCH3H3CO
CH
CH3
CH3
269.3 80.2 425 128-130
The absence of NH2 and C=O absorption bands in the IR spectra confirmed that the
compounds were obtained. The appearance of a medium to strong absorption band at around 1600
cm-1
is due to the stretching vibration of C=N bond formation in the Schiff base compounds. IR
spectral data of 3a-g was depicted in Table 2. The proton spectral data agree with respect to the
number of protons and their chemical shifts with the proposed structures. The proton spectral data
of 1 shows resonance at δ 5.45 ppm (s, 2H, NH2). In all the new compounds, the above resonance
disappeared and additional resonances assigned to the -CH=N- (δ 8.81 – 8.40 ppm) was observed,
which confirmed the products.
Table-2: IR data of Schiff bases 3a-g
Compound
N-H O-H Aromatic C-H C=N C-F C-O C-Cl
1 3392 - 3064 - - - -
3a - - 3081 1601 1302 1155 722
3b - 3419 3082 1606 - 1156 -
3c - 3420 3061 1615 - 1153 -
3d - 3447 3075 1600 - 1158 -
3e - - 3065 1610 - 1152 -
3f - - 3035 1604 - - -
3g - - 3064 1612 - - -
Percentages of DPPH radical scavenging activity was tabulated in Table 3. The in vitro
scavenging assay of DPPH radicals was performed spectrophotometrically [19] with ascorbic acid
as positive control (Figure 1). The percentage scavenging effects of the compound 3b at 100, 150,
200 µg/ml are 57.1, 64.8, 78.1 and compound 3d at 100, 150, 200 µg/ml are 51.1, 60.7, 71.4,
respectively (Fig. 1). The percentage inhibition of the compound 3c at 100, 150, 200 µg/ml are
50.2, 60.4, 70.0, respectively. Ascorbic acid presented a scavenging effect of 98.2 % at the
concentration of 200 µg/ml. The moderate inhibition of 3e and 3f showed 64.5 %, 63.8 % and 64.1
% at 200 µg/ml. Compounds, 3a and 3g exhibited lower inhibition.
Table-3: DPPH radical scavenging activity of the tested compounds
Electron donating hydroxyl group in 3b and 3d showed more antioxidant activity.20
The
hydroxyl group in 3b produces enhanced activity probably by o-position compared to the p-
position in 3d. This indicates the positional requirement of hydroxy group on phenyl ring for
enhanced activity. The compound 3c showed good radical inhibition activity due to the presence of
hydroxyl group and methoxy group in the aromatic ring.21,22
Compound 3g bear a methoxy groups,
3e bearing an electron donating ethoxy group at para position showed similar antioxidant activity.
The aromatic ring system with halogens in 3a was found to be less active than 3g.
Compound Scavenging effect (%)
Concentration of the tested compounds (µg/ml)
100 150 200
3a 30.1 40.5 48.8
3b 57.1 64.8 78.1
3c 50.2 60.4 70.0
3d 51.1 60.7 71.4
3e 42.2 54.8 64.5
3f 42.2 53.0 64.1
3g 30.2 40.0 48.3
Ascorbic acid 73.0 85.3 98.2
Fig. 1
CONCLUSION
In conclusion, a series of new 3,5-dimethoxyaniline derivatives 3a-g were prepared in good
yield, characterized by different spectral studies and their antioxidant activity have been evaluated.
Compounds 3b, 3c and 3d demonstrated good antioxidant activity. The structural activity
relationship studies reveal that, the substituents on phenyl ring are responsible for antioxidant
activity. On the basis of their activity, these derivatives were identified as viable leads for further
studies.
This part of work has been published in Journal of Applicable Chemistry, 2014, 3 (5):
2131-2137. In this article we have shown the antioxidant activities of 3,5-Dimethoxyaniline
Derivatives. All the compounds showed DPPH radical scavenging activity.
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Synthesis and characterization of chromium(III) complexes of 4(3H)-quinazolinone-derived
Schiff base: Antimicrobial studies
Introduction
Transition metal complexes of Schiff bases have attracted much attention due to their potent
biological activities such as antifungal, antibacterial, anticancer and herbicidal applications [1].
Investigations on the interaction between transition metal complexes and DNA have created
interests due to their importance in cancer therapy and molecular biology [2].
In the present work, we describe the synthesis and antimicrobial, abilities of Cr (III) complexes
with a Schiff base ligand derived from3-amino-2-methyl-4(3H)-quinazolinone.
Material and Methods
Chemicals used: 3-amino-2-methyl-4(3H)-quinazolinone and 2-benzofuran carboxaldehyde was
obtained from Aldrich. Chromium(II) salts and solvents were commercially available of high
purity.
Synthesis of 3-(isobenzofuran-1-ylmethyleneamino)-2-methylquinazolin-4(3H)-one (L)
A 1:1 equimolar solution of 3-amino-2-methyl-4(3H)-quinazolinone (0.350 g, 2 mmol) and 2-
benzofuran carboxaldehyde (0.263 g, 2 mmol) were mixed in 30 mL methanol and gently heated
for 3 h with constant stirring. The characteristic yellow precipitate of Schiff base obtained by
condensation was filtered and crystallized using ethanol.
Yield: 83%, IR (nujol mulls, cm-1): 3088.4, 2924.5, 2161.8 (C-H), 1684.2 (C=O), 1597.0 (C=N),
1H-NMR (400 MHz, DMSO-d6) δ: 2.72 (s, CH3, 3H, C8), 8.9 (s, CH, 1H, N=CH-), 7.4-8.2 (m,
Ar-H, 8H, Aromatic protons), Mass (m/z): 265 [M++1], Anal: Calcd. For C15H12N4O: C 68.18,
H 4.28, N 21.22, Found: C 68.27, H 4.3, N 21.32 %. Based on these data, the following molecular
structure has been assigned to the Schiff base (Figure 1).
Figure1:Structure of 3-(isobenzofuran-1-ylmethyleneamino)-2-methylquinazolin-4(3H)-one (L).
Synthesis of metal complexes
The Cr(III) complexes of Schiff base ligand were prepared in 1:2 [metal:ligand] and 1:1:1
[metal:ligand:1,10-phenanthroline] ratios.
To a 20 ml hot methanolic solution of metal chloride (0.170 g, 1 mmol), Schiff base ligand
solution was added (L, 2 mmol) to obtain 1:2 complex and a methanolic solution of 1,10-
phenanthroline (0.198 g, 1 mmol) was added slowly in the presence of 1 mmol of L with
continuous stirring to obtain 1:1:1 complex. The resulting mixture was stirred under reflux for 4
h to obtain the precipitated complex. It was collected by filtration, washed with hot water, then
diethyl ether and dried in air.
Result and discussion
The Schiff base ligand was obtained by the 1:1 condensation of 3-amino-2-methyl-4(3H)-
quinazolinone with 2-pyridine carboxaldehyde. The formation of the Cr(III) complexes was
achieved by reaction of the ligand with Cr(III) salts in 1:2 [M:L] and 1:1:1 ratio. The analytical
and physical data are presented in Table 1.
Table 1: Analytical and physical data of the Cr(III) complexes.
Compound
Molecular
formula
Yield
(%)
Calcd. (found), %
µeff
B.M.
Molar
conductance
Ω-1
cm2mol
-1 C H N M
1 C36H30N6O6ClCr 66 59.25
(59.49)
4.12
(4.17)
11.50
(11.91)
7.10
(7.27)
3.78 12.5
2 C30H25N5O4ClCr 61 59.40
(59.57)
4.12
(4.26)
11.55
(11.79)
8.58
(8.82)
3.75 14.2
IR spectra of Cr(III) complexes:
Important IR spectral bands of Cr(III) complexes.
Compound ν(C=N) ν(C=O) ν(M-O) ν(M-N)
L 1597 1684 --- ---
1 1587 1642 467 565
2 1582 1648 474 537
Conductivity measurements
The molar conductance values of the Cr(III) complexes in DMF (10-3
M solutions) were measured
at room temperature and the results are listed in Table 1. The conductance values of Cr(III)
complexes fall in the range 14.5-12 Ohm-1
cm2mol
-1, indicating the non-electrolytic nature of
complexes (Geary 1971).
The electronic absorption spectra of the Schiff base metal complexes in DMF were recorded at
room temperature. Both the complexes 1 and 2 exhibit an absorption band in the range 360-390
nm, which are assigned to charge transfer transition from the pπ-orbitals of the donor atoms to the
d-orbitals of the metal. In addition, complexes exhibit d-d transition in the 617-724 nm range.
Biology activity
Antimicrobial activity
The data pertaining to the antimicrobial potential of ligand and its Cr(III) complexes are presented
in Table 3. The ligand has poor activity against both bacteria and fungi. This activity may be due
to the presence of imine group which imparts in elucidating the mechanism of transformation
reaction in biological systems. The results indicate that the complexes show more activity than the
ligand against same microorganisms under identical experimental conditions. This would suggest
that the chelation could facilitate the ability of a complex to cross a cell membrane and can be
explained by Tweedy‟s chelation theory. All the test compounds show lesser activity than the
standard antibiotics.
Table 3: Antimicrobial activity of Schiff base and its Cr(III) complexes.
Compound
Zone of inhibition (in mm)*
Antibacterial activity Antifungal activity
S.aureus E.coli A.niger F.oxysporum
L 07 09 03 07
1 18 19 16 23
2 21 23 19 27
Chloramphenicol 32 29 - -
Griseofulvin - - 27 36
*average of three replicates
Conclusion
Based on the data obtained, following structures are assigned for the complexes.
Figure 3: Structures of chromium(III) complexes.
References
1. Liu T., Lv J., Cai S., Wang X., Liu L., Wang Y., J. Inorg. Biochem., 100,1888-1896 ( 2006).
2. Singh K., Barwa M. S., Tyagi P., Eur. J. Med. Chem.,42,394-402 (2007).
ACKNOWLEDGEMENTS
I am grateful to UNIVERSITY GRANT COMMOSSION, Bahadur shah Zafar Marg, New
Delhi for giving me an opportunity to carry out this project work and for the financial assistance.
Annexure-VIII
Submission of information on the final report of the work done on the project
1 Name and address of the Principal
Investigator
Dr.B.K.Kendagannaswamy
Assistant Professor, Dept.of Chemistry.
JSS College of Arts, Commerce and Science
Ooty road, Mysore-25
2 Name and address of the Institution JSS College of Arts, Commerce and Science
Ooty road, Mysore-25
3 UGC approval No and date MRP(S)-1127/11-12/KAMY013/UGC-SWRO
4 Date of implementation 20-07-2012
5 Tenure of the Project 18 Months with Extension
6 Total grants released Rs 1,50,000/-
7 Total grants received Rs 1,42,000/-
8 Final expenditure Rs 1.52,506/-
9 Title of the Project Synthesis and characterization of biologically active metal
complexes
10 Objectives of the Project Synthesis of ligands and synthesis of complexes. Characterization
of the synthesized ligands and complexes. Study of the biological
activity of the ligands and complexes
11 Whether the objectives were achieved YES
12 Achievements from the Project Two papers were published
13 Summary of the findings Schiff bases have a significant role as ligands. The importance of
Schiff bases and their metal complexes are important as
biochemical, electrochemical, analytical, and redox catalysts.
Apart from this they show antifungal and antibacterial activities
as evident from the present work. The molecules synthesized
were purified and they are characterized by IR and NMR. The
molecules show very good antioxidant activity. The scope of the
work is very large as we can synthesize still many more different
ligands and complexes.
14 Contribution to the society In the present project we have synthesized new series of ligands
and metal complexes. These compounds (ligands) show good
antioxidant property. The ligands which are synthesized can be
used to synthesize metal complexes with other transition metals
also.. So it is of great biological importance. The transition metal
complexes play an important role in cancer therapy and
molecular biology
15 Whether any Ph.D enrolled/ produced out
of the project.
Students can be registered for their Ph.D. As soon as I get
recognized as guide, from university of Mysore I will take up the
work of guiding them using the ligands that I have synthesized
for the formation of complexes with different metals.
16 No. of publications out of the Project Two Papers published
Dr.B.K.KENDAGANNASWAMY Prof.M.B.MALLIKARJUNA PANDITH
PRINCIPAL INVESTIGATOR PRINCIPAL